Chapter 14 - Diagnosis of multiple sclerosis

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Abstract

This chapter will serve as a guide for the diagnosis of multiple sclerosis (MS). Primary aims include a review of both the common and atypical clinical manifestations of MS, a detailed discussion of the alternative diagnoses which can mimic MS, as well as a review of the current established diagnostic criteria and a history of their development. It will also review the distinct disease courses and MS variants. The goal of the chapter is to facilitate the diagnostic process for clinicians so that they may expedite early diagnosis and treatment in an effort to alter disease outcomes and ultimately improve patients’ quality of life.

Introduction

In the absence of pathognomonic symptomatology or definitive laboratory tests, multiple sclerosis (MS) continues to pose a diagnostic challenge to clinicians. Dating back to the observations of Jean-Martin Charcot (1868), the diagnosis of MS has required the presence of multiple white-matter lesions in the central nervous system (CNS) that are disseminated in both space and time. Evidence for the presence of such white-matter lesions can be based on clinical history, on neurologic examination, or on paraclinical data such as that from magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, or the recording of evoked potentials. Clinical evidence for dissemination in space can be derived from neurologic examination demonstrating abnormalities indicative of involvement of at least two separate areas in the CNS. Furthermore, a history of two or more clinical attacks (exacerbations) provides definitive clinical evidence for dissemination in time. Frequently, however, history and examination fail to meet diagnostic criteria, resulting in the need for paraclinical data to provide supportive evidence of the diagnosis. Consequently, clinicians must be well versed in both the common and uncommon clinical manifestations in order to diagnose MS properly. Because the diagnosis requires the exclusion of alternative disorders, clinicians must also have a broad knowledge of the differential diagnostic entities that can mimic MS. Moreover, they should be familiar with the current established diagnostic criteria defined by international expert consensus (Polman et al., 2011) and their application in clinical practice.

The ultimate goal for clinicians should be to establish an accurate diagnosis as early as possible. With the continuing emergence of effective therapies, early diagnosis can permit the expeditious initiation of disease-modifying treatments with the primary goal of altering the long-term disease course and improving patients’ quality of life.

Section snippets

Clinical manifestations

The common clinical features of MS have been reviewed by numerous previous authors (Muller, 1949, Kurtzke, 1970, Matthews, 1985, Paty, 2000). Nevertheless, even with such widespread knowledge about MS, approximately 5–10% of patients diagnosed with MS do not actually have the disease (Herndon and Brooks, 1985, Engell, 1998), underscoring the need for clinicians to be cautious. Because of the protean nature of its potential clinical manifestations of CNS dysfunction, MS can present with symptoms

Diagnostic criteria

The diagnostic criteria for MS have continued to evolve over the past 40 years, beginning with Schumacher et al.’s initial scheme established in 1965. This classification (Table 14.2) identified patients as “clinically definite, probable or possible” MS. In addition to the requirement of dissemination in space and time, these criteria included the onset between ages 10 and 50, the presence of objective neurologic signs, predominant evidence of CNS white-matter disease, and the exclusion of

MS courses and variants

Once the diagnosis is made, the type of MS should be categorized because disease course often dictates the appropriate therapy. In 1996, definitions for the most common clinical patterns were proposed (Lublin and Reingold, 1996) (Fig. 14.2). Four types of patterns were described: relapsing-remitting (RR) MS, secondary progressive (SP) MS, primary progressive (PP) MS, and progressive-relapsing (PR) MS. Patients with RRMS, which accounts for approximately 85% of MS patients at onset, experience

Differential diagnosis

The differential diagnosis of MS is extensive and includes infectious, inflammatory, toxic-metabolic, genetic, neoplastic, neurodegenerative, and vascular etiologies. While several of these disease processes share common clinical and paraclinical features with MS, unique differences may facilitate narrowing the diagnostic possibilities (Miller et al., 2008). In the absence of stigmata reflecting other disorders, it is arguable whether any laboratory investigations are warranted in patients

Conclusion

While the differential diagnosis of MS can be extremely challenging to clinicians, a detailed history, neurologic examination, and careful review of imaging and laboratory studies are the most important means to narrow diagnostic considerations and tailor an appropriate workup. The presence of atypical historic, clinical, and paraclinical findings should alert physicians to the prospect of an alternative diagnosis and need for further evaluations. At follow-up, the diagnosis of possible or

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